JP7690216B2 - BIOIMPLANTED ULTRAVIOLET IRRADIATION DEVICE AND BIOIMPLANTED ULTRAVIOLET IRRADIATION SYSTEM - Google Patents

Description

The present invention relates to a bioimplantable ultraviolet irradiation device that can be used for cancer treatment and a bioimplantable ultraviolet irradiation system using the same.

The incidence and mortality rates of cancer are still on the rise. Types of cancer with high mortality rates include lung cancer, breast cancer, liver cancer, colon cancer, stomach cancer, and leukemia, and there is a demand for further development of medical technology. Cancer treatment methods are mainly broadly divided into chemotherapy using anticancer drugs, radiation therapy using electromagnetic waves or particle beams, surgical procedures such as open surgery, endoscopic surgery, and laparoscopic surgery, and transplantation procedures such as hematopoietic stem cell transplantation and bone marrow transplantation, but all of these are highly invasive and have side effects, and are also physically demanding.

The inventors focused on light energy as a therapeutic method that is minimally invasive, has few side effects, places little physical burden on the body, and is inexpensive, and sought a technology that can highly induce apoptosis (cell death) in cancer cells using light energy while suppressing the induction of necrosis. If it is possible to increase the occurrence of apoptosis (cell death) while suppressing the occurrence of necrosis, it is possible to effectively reduce the number of cancer cells while avoiding the occurrence of inflammation due to cancer treatment.
As a result of the inventor's research, it was discovered that by irradiating cancer cells with light in a specific ultraviolet range at an appropriate intensity, it is possible to highly induce apoptosis in cancer cells and suppress the induction of necrosis.

Although some bioimplantable light irradiation devices have been proposed, such as in Patent Document 1, no proposals have been made yet that are effective against cancer cells.

JP 2019-092532 A

The problem that the present invention aims to solve is to provide a bioimplantable ultraviolet irradiation device that can perform cancer treatment that is minimally invasive, has few side effects such as inflammation, and places a minimal burden on the patient.

The bioimplantable ultraviolet irradiation device according to aspect 1 of the present invention comprises a receiving coil for receiving wireless power, an ultraviolet light emitting element that emits ultraviolet light using the power generated by the receiving coil, and a housing that holds the receiving coil and the ultraviolet light emitting element in a state in which the ultraviolet light emitted by the ultraviolet light emitting element can be released to the outside, and the ultraviolet light emitting element has a peak emission wavelength between 300 nm and 400 nm.

According to this bioimplantable ultraviolet irradiation device, the bioimplantable ultraviolet irradiation device is implanted in the living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to the cancer cells, and power is generated in the power receiving coil from an external wireless power supply device, and ultraviolet light is generated from the ultraviolet light emitting element using this power and irradiated to the cancer cells. This induces high apoptosis in the cancer cells and suppresses the induction of necrosis, allowing for cancer treatment that is minimally invasive, has few side effects such as inflammation, and places a low burden on the patient.

The bioimplantable ultraviolet irradiation device according to aspect 2 is the same as that of aspect 1, in which the ultraviolet light emitting element is a light emitting diode having a peak emission wavelength between 330 nm and 395 nm, and therefore it is possible to effectively induce apoptosis in various cancer cells and suppress the induction of necrosis, thereby enabling cancer treatment to be performed with minimal invasiveness, fewer side effects such as inflammation, and less of a burden on the patient.
In the experimental results described below, the effectiveness was confirmed for breast cancer, skin cancer, stomach cancer, and leukemia, but since the inventor's experiments have confirmed that cancer cells generally absorb ultraviolet light of specific wavelengths, it can be assumed that the present invention will have a similar effect on any other cancer cells (e.g., colon cancer, esophageal cancer, liver cancer, prostate cancer, uterine cancer, etc.).

The bioimplantable ultraviolet irradiation device according to aspect 3 is the same as that according to aspect 1 or 2, in which the housing is made of amorphous fluororesin and has a cylindrical shape with both ends sealed. The outer diameter of the housing is 2.9 mm or less.

The housing is made of amorphous fluororesin and has a cylindrical shape with both ends sealed, so that it can be easily inserted into the body along the longitudinal direction of the housing, and the housing is highly waterproof, so the internal structure of the device can be protected for a long period of time. Although amorphous fluororesin is optimal in that it has the least effect on the body, other materials such as polypropylene, polyethylene, and polycarbonate can also be used with minimal invasiveness. The shape of the housing may be cylindrical, square prism, or hexagonal prism, and the tip of the housing may be sharpened into a cone or pyramid shape. If it is sharp, it may be easier to insert into the affected area.

The outer diameter of the housing is 2.9 mm or less, preferably 2.8 mm or less, so that it can be inserted into the treatment tool storage space (inner diameter 2.9 mm) at the tip of a typical endoscope, and by operating the endoscope, the bioembedded ultraviolet irradiation device can be pushed out of the treatment tool storage space at the tip and inserted into the affected area with high positional accuracy, or removed from the affected area. A dedicated insertion tool or removal tool, described later, may be used instead of the endoscope.

The housing is made of a flexible material, so it may be bent midway in the longitudinal direction into a dogleg or arc shape before being inserted into the affected area, or it may be given a shape memory effect so that it is straight when inserted with an endoscope or tool, and curved inside the body after being inserted into the affected area. This makes it possible to set the receiving coil in a direction suitable for receiving power. It is also possible to prevent the coil from being displaced from the affected area by bending or curving. To prevent displacement from the affected area, a convex or concave portion may be formed on the outer circumferential surface of the housing. The convex or concave portion may be a ring-shaped portion coaxial with the central axis of the housing, or a spiral shape. In the case of a spiral shape, the bioimplantable ultraviolet irradiation device may be rotated using an endoscope or tool and screwed into the affected area.

The bioimplantable ultraviolet irradiation device according to aspect 4 is any one of aspects 1 to 3, and includes a control circuit within the housing that receives an AC current from the receiving coil and supplies a DC current or a DC pulse current within a forward voltage range capable of lighting the ultraviolet light emitting element to the ultraviolet light emitting element.

According to this bioimplantable ultraviolet irradiation device, the control circuit receives an AC current from the receiving coil, rectifies and adjusts the voltage, and supplies a DC current or a DC pulse current in a forward voltage range capable of lighting the ultraviolet light emitting element to the ultraviolet light emitting element, so that the ultraviolet light emitting element can emit light stably continuously or in pulses. When emitting light in pulses, the peak emission intensity can be increased compared to the power generated by the receiving coil of the ultraviolet light emitting element.

The bioimplantable ultraviolet irradiation system of aspect 5 of the present invention includes a bioimplantable ultraviolet irradiation device of any one of aspects 1 to 4, and a wireless power supply device for wirelessly supplying power from outside the body to the power receiving coil, and the wireless power supply device uses any one of the following power supply methods: electromagnetic induction, magnetic field resonance type electromagnetic induction, and electromagnetic wave.

According to this bioimplantable ultraviolet irradiation system, a bioimplantable ultraviolet irradiation device is implanted in a living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to cancer cells, and the wireless power supply device generates power from the receiving coil from outside the body using any of the power supply methods of electromagnetic induction, magnetic field resonance type electromagnetic induction, and electromagnetic wave, and the ultraviolet light emitting element generates ultraviolet light using this power and irradiates the cancer cells. This induces high apoptosis in cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment to be performed with minimal invasiveness, fewer side effects such as inflammation, and less of a burden on the patient. The wireless power supply device may be a stationary or portable device. In the case of a portable device, it may be equipped with a battery, a control circuit that generates an alternating current using the power of the battery, and a power transmission coil that generates magnetic force or electromagnetic waves using the control circuit.

According to this bioimplantable ultraviolet irradiation device, the bioimplantable ultraviolet irradiation device is implanted in the living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to the cancer cells, and power is generated in the power receiving coil from an external wireless power supply device, and ultraviolet light is generated from the ultraviolet light emitting element using this power and irradiated to the cancer cells. This induces high apoptosis in the cancer cells and suppresses the induction of necrosis, allowing for cancer treatment that is minimally invasive, has few side effects such as inflammation, and places a low burden on the patient.

1 is a side cross-sectional view of a biological implantable ultraviolet irradiation device according to a first embodiment of the present invention. FIG. 4 is a side cross-sectional view of a biological implantable ultraviolet irradiation device according to a second embodiment of the present invention. FIG. 2 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to an embodiment of the present invention. FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. 1 is a cross-sectional view showing a state in which the biological implantable ultraviolet irradiating device of the first embodiment is used. FIG. FIG. 11 is a side cross-sectional view of a biologically implantable ultraviolet irradiation device according to a third embodiment of the present invention. FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. FIG. 13 is a side cross-sectional view of a biological implantable ultraviolet irradiation device according to a fourth embodiment of the present invention. FIG. 13 is a side cross-sectional view of a biologically implantable ultraviolet irradiation device according to a fifth embodiment of the present invention. FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. FIG. 11 is a plan view illustrating an example of a power transmission coil according to another embodiment of the present invention. 1 is a plan view showing a state in which the biological implantable ultraviolet irradiating device is set in an insertion jig for the biological implantable ultraviolet irradiating device. FIG. 11 is a plan view showing a state in which the biological implantable ultraviolet irradiating device is pushed out from an insertion jig for the biological implantable ultraviolet irradiating device. FIG. 10 is a cross-sectional view showing a state in which the biologically embedded ultraviolet irradiation device is inserted into cancer cells from the insertion tool. FIG. 11 is a cross-sectional view showing a state in which the insertion jig is pulled out after the biological implantable ultraviolet irradiating device is inserted. FIG. FIG. 2 is a plan view of a removal jig for the biological implantable ultraviolet irradiation device. FIG. 13 is a plan view of the removal jig with the locking claws protruding from the tip. 11 is a cross-sectional view of a state in which a biologically embedded ultraviolet irradiation device inside a living body is grasped by a removal jig. 11 is a cross-sectional view of a state in which the bioimplantable ultraviolet irradiation device is being pulled out of a living body by a pulling tool. FIG. 1 is a graph showing an example of the wavelength spectrum of ultraviolet light emitted by an ultraviolet light emitting element used in a biological implantable ultraviolet irradiation device. FIG. 1 is a perspective view showing a test device for comparing the effects of irradiating cancer cells with ultraviolet light to kill the cancer cells. 1 is a graph comparing the rates of apoptosis and necrosis induced in cancer cells when the wavelength and total dose of ultraviolet light were changed. 1 is a graph comparing the survival rate of cancer cells when the wavelength and total amount of ultraviolet light irradiation are changed. 1 is a graph comparing the apoptosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. 1 is a graph comparing the necrosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. 1 is a graph comparing the rates of apoptosis and necrosis induced in cancer cells when the wavelength and total dose of ultraviolet light were changed. 1 is a graph comparing the survival rate of cancer cells when the wavelength and total amount of ultraviolet light irradiation are changed. 1 is a graph comparing the apoptosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. 1 is a graph comparing the necrosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. 1 is a photograph showing samples of colon cancer cells, gastric cancer cells, and breast cancer cells used in the experiment. 1 is a graph showing the apoptosis rates of colon cancer cell, gastric cancer cell, and breast cancer cell samples used in the experiment when not irradiated with ultraviolet light and when irradiated with 30 J/cm ² of ultraviolet light. This is a graph showing the cell survival rate of healthy cells (human skin fibroblasts) when they were not exposed to ultraviolet light and when they were exposed to 10, 20, and 30 J/ ^cm2 . This is a graph showing the cell mortality rate of healthy cells (human skin fibroblasts) when they were not exposed to ultraviolet light and when they were exposed to ultraviolet light at 10, 20, and 30 J/ ^cm2 . These are optical microscope images (100x) showing healthy cells (human skin fibroblasts) not exposed to UV light and exposed to 10, 20, and 30 J/cm2. 1 is a photograph of a prototype implantable ultraviolet irradiation device. This is a photograph of the prototype bioimplantable ultraviolet irradiation device when illuminated.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
[Bio-implantable ultraviolet irradiation device according to the first embodiment]
1 is a side cross-sectional view showing a first embodiment of a bioimplantable ultraviolet irradiating device according to the present invention. This bioimplantable ultraviolet irradiating device 1 has a power receiving coil 2 for receiving wireless power, a control circuit 4 for generating a direct current from an alternating current generated by the power receiving coil 2, an ultraviolet ray emitting element 6 for emitting ultraviolet ray by the direct current from the control circuit 4, and a housing 10 for accommodating these.

The receiving coil 2 is formed by winding 2B by winding a conductive wire of copper or aluminum or the like with an insulated surface in a spiral shape many times around a cylindrical bobbin 2A, and generates an AC current of the same frequency as the transmitting coil 31 by induced electromotive force when it receives magnetic flux generated by the transmitting coil 31 described later. The receiving coil 2 in this embodiment is arranged coaxially with the housing 10, and the thickness, number of turns, and winding pitch of the conductive wire of the winding 2B are appropriately set according to the frequency and strength of the AC current supplied to the transmitting coil 31. The bobbin 2A may be made of a material such as a non-magnetic plastic if the frequency of the AC magnetic flux received by the receiving coil 2 is high, or may be made of a magnetic material such as ferrite if the frequency of the AC magnetic flux received by the receiving coil 2 is low.

The control circuit 4 converts the AC current generated by the receiving coil 2 into a DC current or DC pulse current that can cause the ultraviolet light emitting element 6 to emit light, and various types can be adopted as follows.
(1) The AC current from the receiving coil 2 is simply half-wave or full-wave rectified by a rectifying element such as a diode, and is supplied as is to the ultraviolet light-emitting element 6 as a pulsating DC current. It is preferable to have a current control resistor or an overcurrent protection circuit to protect the ultraviolet light-emitting element 6 from an overcurrent. The peak voltage of the pulsating current must exceed the light-emitting voltage of the ultraviolet light-emitting element 6. In this case, the ultraviolet light-emitting element 6 emits pulsed light in synchronization with the frequency of the magnetic flux generated by the transmitting coil 31.

(2) The AC current from the receiving coil 2 is half-wave or full-wave rectified by a rectifying element such as a diode, and is smoothed to some extent by a capacitor to supply the DC current with ripples to the UV light-emitting element 6. The peak voltage of the DC current must exceed the emission voltage of the UV light-emitting element 6. In this case, the UV light-emitting element 6 emits light continuously.

(3) The AC current from the receiving coil 2 is half-wave or full-wave rectified by a rectifying element such as a diode, and is supplied to the ultraviolet light emitting element 6 as a DC current or a DC pulse current whose voltage has been increased by a known boost circuit. The peak voltage of the DC current must exceed the light emission voltage of the ultraviolet light emitting element 6. In this case, even if the AC voltage from the receiving coil 2 is low, the boost circuit can increase the light emission voltage required by the ultraviolet light emitting element 6. If the AC current from the receiving coil 2 does not provide enough power to make the ultraviolet light emitting element 6 emit light continuously, it may be converted to a DC pulse current and PWM control may be performed to automatically lower the duty ratio, which is the pulse width divided by the period, to maintain the output voltage. In this case, the ultraviolet light emitting element 6 emits light continuously if the AC power generated by the receiving coil 2 is sufficiently large, and emits pulsed light if the AC power generated by the receiving coil 2 is not sufficient for continuous emission.

3 shows an example of a circuit in which the AC current from the power receiving coil 2 is full-wave rectified by a rectifier circuit 12 such as a diode bridge, and the voltage of the DC boosted by a booster circuit 14 is supplied to the ultraviolet light emitting element 6. The voltage of the DC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.
4 shows an example of a circuit in which the AC current from the power receiving coil 2 is full-wave rectified by a rectifier circuit 12 such as a diode bridge, and the voltage is increased by a pulse control circuit 16 that performs PWM control, resulting in a DC pulse current PC that is supplied to the ultraviolet light emitting element 6. The voltage of the DC pulse current PC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.

(4) The control circuit 4 has a resonant circuit with the AC magnetic flux generated by the receiving coil 2, and may also have the circuits (1) to (3) described above. As the resonant circuit with the receiving coil 2, a capacitor of a predetermined capacity can be connected in parallel with the receiving coil 2. This capacitor may be a fixed-capacity capacitor, or a variable-capacity capacitor that adjusts the resonant frequency within a certain range in response to fluctuations in the frequency received from the transmitting coil 31, or resonance may be achieved using the line-to-line capacitance of the winding 2B of the receiving coil 2.

The ultraviolet light emitting element 6 has an emission wavelength peak in the ultraviolet wavelength range of 300 nm to 400 nm. Experiments by the inventor have shown that irradiating cancer cells with ultraviolet light in this wavelength range highly induces apoptosis in the cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment that is minimally invasive, has fewer side effects such as inflammation, and places less of a burden on the patient. The ultraviolet light emitting element 6 may have an emission wavelength peak between 330 nm and 395 nm, and in this case, experiments by the inventor have confirmed that this is particularly effective in inducing apoptosis in cancer cells selected from breast cancer, skin cancer, stomach cancer, and leukemia.

The ultraviolet light emitting element 6 may be specially designed for the present invention, but it is also possible to use ultraviolet light emitting diodes that are generally available on the market. Generally available ultraviolet light emitting diodes in the UVA1 region include those for 340 nm, 365 nm, 375 nm, 385 nm, 392.5 nm, and 395 nm, with rated voltages of 340 nm: 4.6 to 4.8 V, 365 nm: 3.80 to 3.85 V, 375 nm: 3.40 V, 385 nm: 3.35 V, and 395 nm: 3.30 V, but are not limited to these.

The ultraviolet light emitting element 6 is fixed in the housing 10 by the support 8. A lens 10B that is transparent to the ultraviolet light emitted by the ultraviolet light emitting element 6 is provided in the light emission direction of the ultraviolet light emitting element 6, sealing the tip of the housing 10. If the entire housing 10 is made of a material that is transparent to the ultraviolet light emitted by the ultraviolet light emitting element 6, it is possible to configure it without providing the lens 10B. The rear end of the housing 10 is sealed as the end 10C, and the inside of the housing 10 is kept airtight.

Materials for the housing 10 include resins that are less invasive to the body, and glass and ceramics that are less likely to break. In particular, amorphous fluororesin, which is less invasive, is optimal in that it has little effect on the body, but other materials such as polypropylene, polyethylene, and polycarbonate can also be used. The shape of the housing 10 may be cylindrical, square, or hexagonal, with a cylindrical shape being particularly preferable. The tip of the housing 10 may be hemispherical, or may be sharpened into a cone or pyramid shape. If it is sharp, it may be easier to insert it into the affected area.

When used with an endoscope, the outer diameter of the housing 10 is preferably 2.9 mm or less, and more preferably 2.8 mm or less. In this case, it can be inserted into the treatment tool storage space (usually 2.9 mm inside diameter) at the tip of a typical endoscope, and by operating the endoscope, the bioimplantable ultraviolet irradiation device 1 can be pushed out of the treatment tool storage space at the tip and inserted into the affected area with high positional accuracy. A dedicated insertion tool or removal tool, described later, may be used instead of the endoscope.

Figure 5 is a cross-sectional view of a living body showing a living body implantable ultraviolet irradiation system using the living body implantable ultraviolet irradiation device 1 and a method of using the living body implantable ultraviolet irradiation device 1. This living body implantable ultraviolet irradiation device 1 is inserted into normal cells 20 of a living body by an endoscope or an insertion tool, and is held in a state in which the lens 10B is directed toward cancer cells 24 occurring inside tissue consisting of normal cells 20, or in a state in which the lens 10B is inserted into the cancer cells 24. The number of living body implantable ultraviolet irradiation devices 1 inserted into the affected area is not limited to one, and the required number of devices are inserted into the living body at the required position and angle depending on the size of the affected area including the cancer cells 24.

A compress 30 with an internal power transmission coil 31 is attached and fixed to the surface of the skin 22 corresponding to the affected area with an adhesive or the like. Note that the present invention is not limited to fixing with a compress, and the power transmission coil 31 may be fixed along the skin 22 by any other method. Inside the compress 30, the power transmission coil 31 is arranged in a flat state in an electrically insulated state as shown in FIG. 11, and is connected to the power transmission unit 34 via a cord 32. The power transmission unit 34 has a battery 36, a control circuit 38, and an operation panel 40, and can be carried by the patient on a belt or the like (not shown). The control circuit 38 generates an AC current upon receiving power from the battery 36, and supplies the AC power to the power transmission coil 31 via the cord 32, causing the power transmission coil 31 to generate an AC magnetic flux. Note that the power transmission unit 34 does not necessarily have to be portable, and can also be implemented as a stationary type.

The frequency of the AC magnetic flux generated by the power transmission coil 31 is not limited in the present invention, but is preferably in the range of 10 kHz to 20 MHz, taking into account the power receiving efficiency of the power receiving coil 2.

After the power receiving coil 2 receives an AC magnetic flux and generates an AC current, the AC current is converted to a DC current or a DC pulse current by the control circuit 4 and supplied to the UV light emitting element 6, which emits UV light L continuously or in pulses. The emitted UV light L is irradiated to the cancer cells 24 through the lens 10B, and by continuing this irradiation for a certain period of time, it is possible to highly induce apoptosis in the cancer cells 24 and kill at least a portion of the cancer cells 24, while suppressing the induction of necrosis and minimizing side effects such as inflammation. In addition, since the UV light L penetrates the inside of the cancer cells 24 over a certain distance, it is possible to kill not only a single layer of the cancer cells 24, but also multiple layers of the cancer cells 24. After all or a portion of the cancer cells 24 have been induced to apoptose, the treatment is completed by removing the bioembedded UV irradiation device 1 from the normal cells 20 in the living body using an endoscope or a removal tool described later.

The control circuit 38 estimates the power supplied from the receiving coil 2 to the ultraviolet light emitting element 6 from the state of the alternating current flowing to the transmitting coil 31, and performs feedback control to increase the power supplied to the transmitting coil 31 when the magnetic coupling is poor due to the distance or orientation between the transmitting coil 31 and the receiving coil 2, and to reduce the power supplied to the transmitting coil 31 when the magnetic coupling between the transmitting coil 31 and the receiving coil 2 is good, thereby stabilizing the intensity of ultraviolet light generated by the ultraviolet light emitting element 6. The operation panel 40 switches the control circuit 38 on and off, and adjusts the intensity and frequency of the alternating current supplied to the transmitting coil 31, so that the ultraviolet light emitting element 6 generates ultraviolet light of the required intensity.

The power transmission unit 34 may be equipped with a storage device that records the power value sent from the power transmission coil 31 to the power receiving coil 2 over time, and a communication device that transmits the power value by wireless signal to a recording device outside the power transmission unit 34. In this case, it is possible to quantitatively confirm the treatment effect from the information in the recording device.

[Second embodiment of the bioimplantable ultraviolet irradiation device]
Fig. 2 shows a second embodiment of the bioimplantable ultraviolet irradiating device 1. In this second embodiment, the power receiving coil 2 is different from that in the first embodiment, and the power receiving coil 2 is formed by winding a winding 2B around an elliptical or oval bobbin 2A having an axis perpendicular to the longitudinal direction of the housing 10. The other configurations of the second embodiment are similar to those of the bioimplantable ultraviolet irradiating device 1 in Fig. 1, and therefore the description thereof is incorporated herein.

In this second embodiment, the power receiving coil 2 generates electricity from the magnetic flux from a direction perpendicular to the longitudinal direction of the housing 10, so even when the bioimplantable ultraviolet irradiating device 1 is embedded in a state close to parallel to the skin 22, electricity can be transmitted from the power transmitting coil 31 of the compress 30 attached to the skin 22. Therefore, depending on the angle at which the bioimplantable ultraviolet irradiating device 1 is embedded in the body, it is possible to select and use either the bioimplantable ultraviolet irradiating device 1 in FIG. 1 or the bioimplantable ultraviolet irradiating device 1 in FIG. 2.

[Third embodiment of the bioimplantable ultraviolet irradiation device]
FIG. 6 shows a third embodiment of the bioimplantable ultraviolet irradiation device 1. The third embodiment is characterized in that the control circuit 4 is simplified to reduce the overall size. The receiving coil 2 is coaxially arranged in a housing 10 with a short overall length, and as shown in FIG. 7, the lead wire of the receiving coil 2 is directly connected to the lead wire of the ultraviolet light emitting element 6. As the control circuit, a diode 42 is connected in parallel with the ultraviolet light emitting element 6 in the opposite direction to the ultraviolet light emitting element 6. The diode 42 serves to prevent the ultraviolet light emitting element 6 from being destroyed by a reverse voltage, and the ultraviolet light emitting element 6 generates pulsed light PL in synchronization with the AC magnetic flux supplied from the power transmission coil 31. The peak voltage of the DC pulse current PC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.

The tip of the ultraviolet light emitting element 6 is sharpened into a pyramidal shape by removing the plastic coating, and is exposed from the tip of the housing 10. The rest of the configuration of the third embodiment is the same as that of the bioimplantable ultraviolet irradiation device 1 in FIG. 1, so the description of the first embodiment is used here.

According to the third embodiment, since the overall length of the bioimplantable ultraviolet irradiation device 1 is short, even if the cancer cells 24 are located shallow in the biological tissue, the bioimplantable ultraviolet irradiation device 1 can be easily inserted into the affected area and maintained in its position. In addition, since the tip of the ultraviolet light emitting element 6 is sharp, it has the advantage of being easily inserted into the living body.

[Fourth embodiment of the implantable ultraviolet irradiating device]
8 shows a fourth embodiment of the bioimplantable ultraviolet irradiating device 1. In this fourth embodiment, the housing 10 is bendable at the center portion 10D, and the bioimplantable ultraviolet irradiating device 1 can be bent in a dogleg or curved shape. According to this fourth embodiment, the axial direction of the receiving coil 2 and the optical axis direction of the ultraviolet ray of the ultraviolet ray light emitting element 6 can be changed, so that even if the optical axis of the ultraviolet ray light emitting element 6 is arranged inclined with respect to the surface of the skin 22 in the living body, the axial direction of the receiving coil 2 can be arranged at an angle close to perpendicular to the surface of the skin 22. Therefore, it is possible to improve the efficiency of receiving electricity from the power transmitting coil 31. In addition, according to the fourth embodiment, there is a possibility that the effect that the bioimplantable ultraviolet irradiating device 1 is difficult to come off from the living body can be obtained.

In addition, the housing 10 may be bent at the bending portion 10D before the bioimplantable ultraviolet irradiation device 1 is embedded, or the bending portion 10D may be bent during or after embedding in the body. In addition, the housing 10 may be memorized in a curved or bent shape, and after being embedded in the body through an endoscope, it may be curved or bent to return to the memorized shape.

[Fifth embodiment of a biologically embedded ultraviolet irradiation device]
9 shows a fifth embodiment of the bioimplantable ultraviolet irradiating device 1. In this fifth embodiment, in order to widen the ultraviolet irradiating area from the tip of the bioimplantable ultraviolet irradiating device 1, a first ultraviolet emitting element 6 with an ultraviolet irradiating direction facing forward in the direction of the housing central axis and a plurality of (for example, two to four) second ultraviolet emitting elements 6 with an ultraviolet irradiating direction inclined at a certain angle (90° in the figure) to the housing central axis are arranged at the tip of the housing 10. The second ultraviolet emitting elements 6 are preferably arranged at equal intervals around the housing central axis. The lens 10B has a cylindrical portion with a long U-shaped cross section and is made of a material that transmits ultraviolet light so that the ultraviolet ray L can be emitted at a wide irradiation angle. The first and second ultraviolet emitting elements 6 are connected in parallel or in series to each other and emit ultraviolet rays of the same wavelength at the same time. Lens 10B may be made of a material that does not scatter ultraviolet light, but inner surface 10E and/or outer surface of lens 10B may be a light scattering surface that scatters ultraviolet light emitted by first and second ultraviolet light emitting elements 6, or lens 10B may be formed of a light scattering material that scatters ultraviolet light. When lens 10B has a scattering effect, it is possible to further expand the ultraviolet light irradiation area.

According to the fifth embodiment, the bioimplantable ultraviolet irradiation device 1 emits ultraviolet light over a wide angle from its tip, so that it is possible to increase the area of cancer cells 24 that can be irradiated with ultraviolet light, thereby expanding the area where a therapeutic effect can be obtained.

[Sixth embodiment of a bioimplantable ultraviolet irradiation device]
10 shows a sixth embodiment of the bioimplantable ultraviolet irradiation device 1. In this sixth embodiment, a first ultraviolet light emitting element 6B, a second ultraviolet light emitting element 6C, and a third ultraviolet light emitting element 6D, each of which generates ultraviolet light with a different emission wavelength, are arranged inside the tip of the housing 10, and whichever element emits the ultraviolet light is irradiated to the front of the housing 10 through the lens 10B.

Inside the housing 10, there are provided a rectifier circuit 12 such as a diode bridge that rectifies the AC current from the receiving coil 2, a boost circuit 14 that generates a DC current by increasing the voltage from the rectified DC current, and a switching circuit 43 that switches the boosted DC current or DC pulse current to flow only to one of the first ultraviolet light-emitting element 6B, the second ultraviolet light-emitting element 6C, and the third ultraviolet light-emitting element 6D.

The first ultraviolet light-emitting element 6B, the second ultraviolet light-emitting element 6C, and the third ultraviolet light-emitting element 6D all generate ultraviolet light, but the wavelengths are different; for example, the first ultraviolet light-emitting element 6B emits 340 nm, the second ultraviolet light-emitting element 6C emits 365 nm, and the third ultraviolet light-emitting element 6D emits 385 nm. According to the inventor's experiments, the ultraviolet wavelengths that are more likely to induce apoptosis and less likely to induce necrosis may differ depending on the type of cancer cell, so if ultraviolet light of any suitable wavelength can be selected from the outside and emitted, it will be possible to use it to treat multiple types of cancer.

The switching circuit 43 has a frequency detection circuit that detects the frequency of the AC current from the winding 2B before it is rectified by the rectifier circuit 12. If this frequency detection circuit determines that the frequency is A, it supplies the output power of the control circuit 14 to the first ultraviolet light-emitting element 6B. If it determines that the frequency is B, it supplies the output power of the control circuit 14 to the second ultraviolet light-emitting element 6C. If it determines that the frequency is C, it supplies the output power of the control circuit 14 to the third ultraviolet light-emitting element 6D.

On the other hand, the control circuit 38 of the power transmission unit 34 can set the frequency of the alternating current supplied to the power transmission coil 31 by the operation panel 40 to any one of frequencies A, B, or C. Therefore, according to the sixth embodiment of the implantable ultraviolet irradiation device 1 and the implantable ultraviolet irradiation system using the same, there is an advantage in that the ultraviolet wavelength generated by the implantable ultraviolet irradiation device 1 can be selected from a plurality of types by operating the operation panel 40, and the type of cancer cells to be treated can be selected.

[Insertion tool for implantable ultraviolet irradiation device]
The bioimplantable ultraviolet irradiating device 1 of the present invention can be inserted into the affected area using an endoscope as described above, but it can also be inserted into the affected area using an insertion tool such as those shown in Figures 12 to 15.

As shown in Figs. 12 and 13, the insertion tool 50 has a cylindrical main body 51, a long and thin cylindrical needle 52 extending coaxially from the tip of the main body 51, and a cutting edge 54 formed at the tip of the needle 52, with an opening 56 formed at the base of the cutting edge 54. The inside of the needle 52 has an inner diameter that allows the bioimplantable ultraviolet irradiation device 1 to pass through, and the bioimplantable ultraviolet irradiation device 1 can be removed to the outside through the opening 56. A slidable shaft 58 is coaxially arranged inside the main body 51 and the needle 52. A slit 59 is formed on the circumferential surface of the main body 51, extending from near the rear end of the main body 51 to near the tip, and a knob 60 is attached to the rear end of the shaft 58 through the slit 59. When the knob 60 is tightened, the shaft 58 is fixed to the main body 51 at any position.

To insert the bioimplantable ultraviolet irradiation device 1 into the living body using the insertion tool 50, first fix the knob 60 at the rear end of the slit 59, and then load the bioimplantable ultraviolet irradiation device 1 into the needle 52 through the opening between the front end of the slit 59 and the shaft 58, as shown in FIG. 12. Orient the ultraviolet light emitting element 6 of the bioimplantable ultraviolet irradiation device 1 toward the blade tip 54.

Next, as shown in FIG. 14, the patient is partially anesthetized, and surgical X-ray imaging devices 62 are placed above and below the affected area. While checking the position of the tumor while watching the monitor 64, the needle 52 of the insertion tool 50 is inserted into the living body to the position where the cancer cells 24 are located. In this state, the knob 60 is loosened and the shaft 58 is moved forward along the slit 59, and the bio-implantable ultraviolet irradiation device 1 is pushed out from the opening 56 and inserted into the normal cells 20 at the position where the ultraviolet light from the ultraviolet light emitting element 6 hits the cancer cells 24. When the insertion is completed, the insertion tool 50 is pulled out of the living body as shown in FIG. 15. This insertion operation is repeated to set the required number of bio-implantable ultraviolet irradiation devices 1 at the affected area. Thereafter, the ultraviolet light from the ultraviolet light emitting element 6 is irradiated onto the cancer cells 24 by passing electricity from the power transmission unit 34 to the power transmission coil 31, which induces apoptosis in the cancer cells 24 and suppresses the induction of necrosis, making it possible to perform cancer treatment that is minimally invasive and has few side effects such as inflammation.

[Tool for removing implantable ultraviolet irradiation device]
The bioimplantable ultraviolet irradiating device 1 of the present invention can be extracted from the living body using an endoscope as described above, but it can also be extracted from the living body using an extraction tool 70 as shown in Figures 16 to 19.

16 and 17, the extraction tool 70 has a cylindrical main body 71, an elongated cylindrical needle 72 extending coaxially from the tip of the main body 71, and a cutting edge 74 formed at the tip of the needle 72, with an opening 76 formed at the base of the cutting edge 74. The inside of the needle 72 has an inner diameter that allows the bioimplantable ultraviolet irradiation device 1 to pass through, and the bioimplantable ultraviolet irradiation device 1 can be inserted into the inside through the opening 76. A tube 78 is slidably arranged coaxially inside the main body 71 and the needle 72. A slit 77 is formed on the circumferential surface of the main body 71, and a knob 80 is attached to the rear end of the tube 78 through the slit 77. When the knob 80 is tightened, the tube 78 is fixed to the main body 71 at any position. A pair of locking claws 79 are slidably arranged inside the tube 78. When the locking claws 79 are extended from the tip of the tube 78, the locking claws 79 open, and when the locking claws 79 are pulled back into the tube 78, the locking claws 79 close, allowing the bioimplantable ultraviolet irradiation device 1 to be grasped. The tube 78 is provided with a set screw 82 for fixing the position of the locking claws 79.

To retrieve the bioimplantable ultraviolet irradiation device 1 from the living body using the extraction tool 70, the patient is anesthetized, and as shown in FIG. 18, surgical X-ray imaging devices 62 are placed above and below the affected area, and while checking the location of the tumor by looking at the monitor 64, the needle 72 of the extraction tool 70 is inserted into the living body, with the tip facing the rear end of the bioimplantable ultraviolet irradiation device 1. In this state, the knob 80 is loosened to move the tube 78 forward, the locking screw 82 is loosened to push the locking claw 79 out of the tube 78, and the open locking claw 79 clamps the rear end of the bioimplantable ultraviolet irradiation device 1. Next, as shown in FIG. 19, the locking claw 79 is pulled into the tube 78, the locking claw 79 grips the bioimplantable ultraviolet irradiation device 1, and the locking screw 82 is fixed in this state. Furthermore, the knob 80 is slid toward the rear end to accommodate the bioimplantable ultraviolet irradiation device 1 in the sleeve 72. The implantable ultraviolet irradiation device 1 can then be removed by pulling the removal tool 70 out of the living body.

By using such an insertion tool 50 and extraction tool 70, the bioimplantable ultraviolet irradiation device 1 can be safely and easily inserted into and removed from the body, thereby improving the convenience of the bioimplantable ultraviolet irradiation device 1 and the system.

Although various embodiments of the present invention have been described above, the present invention is not limited to these, and within the scope of the claims, the features of each embodiment may be combined with each other, and configurations that are not essential to the present invention may be removed.

Next, the results of the inventor's experiments on UV irradiation of various cancer cells will be explained, and the effects of the present invention will be described in detail.

Figure 20 is a graph showing the characteristics of commercially available ultraviolet light-emitting elements (ultraviolet light-emitting diodes) used in this experimental example, with the vertical axis representing light intensity (arbitrary units) and the horizontal axis representing wavelength (nm). The respective peak wavelengths were 340 nm, 365 nm, and 385 nm, as specified. The luminous flux/radiant flux of the 340 nm ultraviolet light-emitting element was 70 mW, and the emission voltage was 4.8 V. The luminous flux/radiant flux of the 365 nm ultraviolet light-emitting element was 1200 mW, and the emission voltage was 3.80 V. The luminous flux/radiant flux of the 385 nm ultraviolet light-emitting element was 550 mW, and the emission voltage was 3.35 V.

Figure 21 is a perspective view showing the ultraviolet irradiation device, light emission control device, and computer used in this experiment. The ultraviolet light-emitting diode, which was placed facing downwards in the central ultraviolet irradiation device, irradiated ultraviolet light onto cancer cells in a petri dish placed below. The ultraviolet light-emitting diode was constantly cooled using a cooling fan and a heat sink. Pathogenic cells of cutaneous lymphoma (Jurkat T cells) or skin cancer (melanoma cells) were placed in the petri dish to carry out the experiment.

[Apoptosis/necrosis induction experiment of pathogenic cells (Jurkat T cells) of cutaneous lymphoma]
Jurkat T cells were cultured for 48 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% _CO2 . The grown Jurkat T cells were washed and replaced with PBS medium in 36 petri dishes. Using the device shown in Figure 21, the pathogenic cells in the petri dishes were irradiated with ultraviolet light using the ultraviolet light-emitting diodes of 340 nm, 365 nm, and 385 nm. The irradiation conditions are shown in Table 1.

Because the light-emitting efficiency of ultraviolet light-emitting diodes differs depending on the ultraviolet wavelength, the irradiation distance to the pathogenic cells was adjusted to keep the irradiation intensity constant. As a result, the irradiation intensity, total irradiation amount, and irradiation time in Table 1 were the same for all three wavelengths.

The pathogenic cells after UV irradiation were cultured for 24 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and _CO2 : 5%. After the culture, the pathogenic cells in each dish were stained with the staining reagent Annexin V and the staining reagent PI, and then analyzed by flow cytometry (FACS) using a flow cytometer. If Jurkat T cells are in a normal state where apoptosis is not induced, membrane phospholipids (phosphatidylserine PS) are present inside the cell membrane and there is no damage to the cell membrane, so the reagent PI is not taken up into the cell and does not bind to the nuclear DNA. However, if apoptosis is induced in the pathogenic cells, the apoptotic cells and necrotic cells are stained with both the staining reagent Annexin V and the staining reagent PI, so that quantitative analysis of the apoptotic cells and necrotic cells can be performed by flow cytometry.

22 is a graph showing the results of flow cytometry analysis showing the densities of live pathogenic cells, apoptosis-induced cells, and necrosis-induced cells in cases of irradiation with a total dose of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm. At each wavelength, the number of apoptosis-induced cells increased as the total dose increased, but the number of necrosis-induced cells hardly increased. In addition, the shorter the wavelength, the fewer the final live cells.
Fig. 23 is a graph showing the percentage of viable pathogen cells at total doses of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). The higher the total dose and the shorter the wavelength, the fewer the final viable cells.
24 is a graph showing the percentage (%) of pathogen cells that underwent apoptosis induction when irradiated with total doses of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). At ¹⁰ J/cm2, more than 60% of cells were induced to apoptosis, at 20 J/ ^cm2 , more than 70%, and at 30 J/ ^cm2 , more than 80%. The percentage of cells that underwent apoptosis induction was higher with shorter wavelengths.
25 is a graph showing the percentage (%) of pathogenic cells in which necrosis was induced when exposed to total doses of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). From the control to 30 J/ ^cm2 , the percentage of cells in which necrosis was induced was less than 2%. No particular effect of differences in total dose and wavelength on necrosis induction was observed.

As shown in Figures 22 to 25, in the case of leukemia cells (Jurkat T cells), which are non-adherent cells, the highest apoptosis induction of 97% was observed at a peak wavelength of 340 nm x 30 J/ ^cm2 . On the other hand, necrosis induction was only 2% or less even at a peak wavelength of 340 nm x 30 J/ ^cm2 .

[Apoptosis and necrosis induction experiments in skin cancer (melanoma cells)]
Melanoma cells were cultured for 48 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% _CO2 . The grown melanoma cells were washed and replaced with PBS medium in 36 petri dishes. Using the device shown in Figure 21, ultraviolet light was irradiated onto the pathogenic cells in the petri dishes using ultraviolet light-emitting diodes of 340 nm, 365 nm, and 385 nm. The irradiation conditions were the same as those in Table 1.

The pathogenic cells after UV irradiation were cultured in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% _CO2 for 48 hours. After the culture, the melanoma cells in each dish were stained with Annexin V and PI, and then analyzed by flow cytometry (FACS) using a flow cytometer.

26 is a graph showing the results of flow cytometry analysis showing the density of live cells, apoptosis-induced cells, and necrosis-induced cells of melanoma cells irradiated with a total dose of 0 (control), ¹⁰ J/cm ^{2 , 20 J/cm 2} , and 30 J/cm ² at each wavelength of 340 nm, 365 nm, and 385 nm. At each wavelength, the number of apoptosis-induced cells increased as the total dose increased, but the number of necrosis-induced cells hardly increased. In addition, it was confirmed that the apoptosis-inducing effect was high in the cases of 340 nm and 365 nm among the three wavelengths, and that the apoptosis-inducing effect on melanoma cells was particularly high in the case of 365 nm. In this way, it was confirmed that the absorbance rate of ultraviolet light for each wavelength differs depending on the type of cancer.

27 is a graph showing the percentage of viable melanoma cells irradiated with total doses of 0 (control), 10 J/ ^cm2 , 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). When the total dose was 30 J/ ^cm2 , the survival rate was significantly reduced in the cases of 340 nm and 365 nm.
28 is a graph showing the percentage (%) of apoptotic cells in melanoma cells irradiated with total doses of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , and 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). When the total dose was 30 J/ ^cm2 , the percentage of apoptotic cells reached nearly 100% in the cases of 340 nm and 365 nm.
Figure 29 is a graph showing the percentage (%) of melanoma cells in which necrosis was induced when exposed to light with a total dose of 0 (control), ¹⁰ J/cm2, 20 J/ ^cm2 , or 30 J/ ^cm2 at wavelengths of 340 nm, 365 nm, and 385 nm (Tukey-Kramer test, p<0.05, n=3). In the control, the percentage was 5-6%, but under the conditions of 10 to 30 J/ ^cm2 , the percentage of cells in which necrosis was induced was about 1% or less. There was no particular effect of the difference in total dose and wavelength on necrosis induction among these conditions.

As shown in Figures 26 to 29, in the case of malignant melanoma (skin cancer) cells, which are adherent cells, apoptosis induction of about 95 to 98% was observed at peak wavelengths of 340 nm and 365 nm at 30 J/ ^cm2 . In particular, it was confirmed that the apoptosis induction effect on melanoma cells was high at 365 nm. On the other hand, necrosis induction in these cases was about 1% or less.

As shown by the above results, ultraviolet light in a specific wavelength range is highly effective in inducing apoptosis in cancer cells, while suppressing the induction of necrosis. It was also found that the effective peak wavelength and total irradiation amount differ depending on the type of cancer cell.

[UV irradiation experiments on colon cancer, stomach cancer, and breast cancer pathogenic cells]
We conducted ultraviolet irradiation experiments using human colon cancer, gastric cancer, and breast cancer pathogenic cells. Tumors (spheroids) were created with each pathogenic cell type, assuming a realistic situation. The details of the pathogenic cells are as follows:
Colorectal cancer cells (E-GFP)
Gastric cancer cells (Nawa (N+0))
Breast cancer cells (MCF-7)

Each pathogenic cell was cultured in cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% _CO2 for 96 hours to create a tumor (spheroid). Figures 30(a) to (c) show photographs of each cell after culture in a petri dish, and Figures 30(d) to (f) show microscopic photographs (40x) of the cells.

Using the device shown in Figure 21 and a 365 nm ultraviolet light emitting diode, ultraviolet light was irradiated onto the colon cancer, stomach cancer, and breast cancer tumors in the petri dish. The irradiation conditions were a total irradiation dose of 0 (control) and a total irradiation dose of 30 J/ ^cm2 .
The irradiated tumor cells were further cultured in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% _CO2 for 24 hours, and the tumor was removed from the dish and the cells were loosened. The loosened cells were counted using a hemocytometer to count live cells and apoptosis-induced dead cells, and the results were compared with those of a non-irradiated (control) sample.

Figures 31(a) to (c) are graphs showing the ratio of live cells to dead cells in colon cancer cells (E-GFP), gastric cancer cells (Nawa (N+0)), and breast cancer cells (MCF-7) without irradiation (control), and Figures 31(d) to (f) are graphs showing the ratio of live cells to apoptosis-induced dead cells after irradiation with 30 J/ ^cm2 of UV light.

As shown in FIG. 31, it was found that apoptosis (cell death) was induced in cells that were given a total irradiation dose of 30 J/ ^cm2 compared to non-irradiated cells (control). Comparing colon cancer cells, gastric cancer cells, and breast cancer cells irradiated with a total irradiation dose of 30 J/ ^cm2 , it was found that colon cancer cells were more susceptible to apoptosis induction. On the other hand, it was estimated that 365 nm is not ineffective against gastric cancer cells and breast cancer cells, but that a total irradiation dose higher than the total irradiation dose of 30 J/ ^cm2, which was the condition of this experiment, is required. From these experimental results, it was found that the bioimplantable ultraviolet irradiation device is effective in cancer treatment by obtaining a sufficient total irradiation dose.

[Investigation of the effect of ultraviolet light (365 nm) on human skin fibroblasts]
The following experiment was carried out to confirm that UV irradiation of non-cancerous human skin fibroblast cells would not cause abnormalities in healthy cells.
Human dermal fibroblasts were cultured for 72 hours in a cell growth medium (MEMα+10% FBS) at 37° C. and 5% CO ₂ . The grown human dermal fibroblasts were washed and replaced with PBS medium in 15 petri dishes. Using the device shown in FIG. 21 and a 365 nm ultraviolet light emitting diode, the cells in the petri dishes were irradiated with ultraviolet light. The irradiation conditions are shown in Table 2. Note that sham irradiation refers to a condition in which the cells were left at room temperature for the same time (16.6 min.) as the total irradiation amount of 30 J/cm ² without irradiating with ultraviolet light and with PBS medium added. The effect of PBS medium on the cells was examined under these conditions.

The cells after UV irradiation were cultured in cell growth medium (MEMα + 10% FBS) at 37°C and 5% _CO2 for 72 hours. After culture, the cells in each dish were stained with the staining reagent Acridine Orange/Propidium Iodide Stain and analyzed using an automatic fluorescent cell counter.

32 is a graph showing the ratio (%) of live cells in each sample when the total amount of ultraviolet irradiation was 0 (control), mock irradiation, 10, 20, and 30 (J/cm ² ). The survival rate was close to 100% in all cases.
33 is a graph showing the percentage (%) of dead cells in each sample when the total amount of ultraviolet radiation was 0 (control), mock radiation, 10, 20, and 30 (J/cm ² ). The mortality rate was low, at about 2 to 3%, in all cases.
34(a) to (e) are optical microscope photographs (100x) of human skin fibroblasts in each sample with a total UV irradiation dose of 0 (control), mock irradiation, 10, 20, and 30 (J/ ^cm2 ). No particular differences were observed.

As shown in Figures 32 to 34, no significant difference was observed when comparing the control and mock irradiation. Therefore, it was found that the PBS medium did not have a negative effect on human dermal fibroblasts. In addition, it was found that ultraviolet irradiation at total doses of 10, 20, and 30 J/ ^cm2 did not have a negative effect on human dermal fibroblasts compared to the control. Even at the maximum total dose of 30 J/ ^cm2 , cell death was limited to only about 3%.
These results indicate that the ultraviolet light emitted from the implantable ultraviolet irradiation device has almost no adverse effects on healthy cells.

Figures 35 and 36 are photographs of a bioimplantable ultraviolet irradiation device prototyped by the inventor. Despite its small size (diameter 4.8 mm x total length 12 mm), the ultraviolet light-emitting diode (365 nm) was able to emit light when it received an AC magnetic flux (300 kHz) from the power transmission coil.

According to the bioimplantable ultraviolet irradiation device of the present invention, the bioimplantable ultraviolet irradiation device is implanted in a living body at a position where it can irradiate cancer cells with ultraviolet light emitted by the ultraviolet light emitting element, and power is generated in the power receiving coil from an external wireless power supply device, and ultraviolet light is generated from the ultraviolet light emitting element using this power and irradiated to the cancer cells. This highly induces apoptosis in cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment to be performed that is minimally invasive, has few side effects such as inflammation, and places a low burden on the patient. Therefore, the present invention can be used industrially.

1 Bioimplantable ultraviolet irradiation device 2 Receiving coil 2A Bobbin 2B Winding 4 Control circuit 6 Ultraviolet light emitting element 6A Tip 6B First ultraviolet light emitting element 6C Second ultraviolet light emitting element 6D Third ultraviolet light emitting element 8 Support 10 Housing 10A Housing main body 10B Lens 10C End 10D Bending portion 12 Rectifier circuit 14 Control circuit 16 Pulse control circuit 20 Normal cells 22 Skin 24 Cancer cells L Ultraviolet light 30 Compress 31 Power transmission coil 32 Cord 34 Power transmission unit 36 Battery 38 Control circuit 40 Operation panel 42 Diode 43 Switching circuit 50 Insertion jig 51 Main body 52 Needle 54 Cutting edge 56 Opening 58 Shaft 59 Slit 60 Knob 62 Position measurement unit 64 Monitor 70 Removal jig 71 Main body 72 Needle 74 Cutting edge 76 Opening 78 Tube 79 Engagement claw 80 Knob 82 Setscrew

Claims (5)

a biological implantable ultraviolet irradiation device comprising: a receiving coil for receiving wireless power supply; an ultraviolet light emitting element for emitting ultraviolet light using power generated by the receiving coil; and a housing for holding the receiving coil and the ultraviolet light emitting element in a state in which the ultraviolet light emitted by the ultraviolet light emitting element can be released to the outside, the ultraviolet light emitting element having an emission wavelength peak between 340 nm and 385 nm; and a wireless power supply device for wirelessly supplying power to the receiving coil from outside the body;
the wireless power supply device is a power supply system using any one of an electromagnetic induction system, a magnetic field resonance type electromagnetic induction system, and an electromagnetic wave system;
The wireless power supply device wirelessly supplies power to the receiving coil so that the total irradiation amount of the ultraviolet rays from the ultraviolet light emitting element is 10 to 30 J/ ^cm2 . The bioimplantable ultraviolet irradiation system according to claim 1, characterized in that the housing is made of a flexible material, and the bioimplantable ultraviolet irradiation device is bendable midway along the length of the housing. The bioimplantable ultraviolet irradiation system according to claim 1 or 2, characterized in that the housing is made of amorphous fluororesin, has a cylindrical shape with both ends sealed, and has an outer diameter of 2.9 mm or less. The bioimplantable ultraviolet irradiation system according to claim 1 or 2, characterized in that a plurality of ultraviolet light emitting elements that generate ultraviolet light with different emission wavelengths are arranged in the housing, and a switching circuit is provided that selects one of the ultraviolet light emitting elements and supplies the power generated by the receiving coil. 3. The implantable ultraviolet irradiation system according to claim 1, wherein the tip of the implantable ultraviolet irradiation device is sharpened in a conical or pyramidal shape, and the ultraviolet light from the ultraviolet light emitting element is emitted from the sharp tip.

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